This is an application for a K23 award for Dr. Lucian Davis, a pulmonary/critical care physician at the University of California, San Francisco (UCSF). Dr. Davis is establishing himself as an investigator in patient-oriented clinical research on novel diagnostics for HIV-associated tuberculosis in high-burden, resource-limited settings (RLS). This K23 award will provide Dr. Davis with the support necessary to accomplish the following goals: (1) to become expert at patient-oriented clinical research into improved diagnostic and prognostic tests for TB in patients with HIV; (2) to learn to apply laboratory research techniques for nucleic acid amplification to clinical specimens; (3) to learn to apply advanced biostatistical methods for evaluating diagnostic and prognostic tests; and (4) to learn to apply advanced analytic methods for evaluating the efficacy and cost effectiveness of diagnostic tests; and (5) to develop an independent clinical research career. To achieve these goals, Dr. Davis has assembled a mentoring team comprised of a primary mentor, Dr. Laurence Huang, Professor of Medicine at UCSF and an internationally recognized expert researcher in HIV-associated pulmonary diseases; and two co-mentors: Dr. Philip Hopewell, Professor of Medicine at UCSF and an internationally recognized authority on global TB control; and Dr. Dennis Osmond, Professor of Epidemiology and Biostatistics at UCSF, and an expert epidemiologist in the field of HIV and its respiratory complications. A lack of rapid, sensitive, affordable diagnostics for TB is a major limitation to global control of the disease, especially in high HIV-prevalence areas. Dr. Davis' research will determine if a widely available DMA test for Mycobacterium tuberculosis paired with a novel specimen, the oral wash, is more accurate for diagnosis of TB in HIV-infected patients than the current standard test, sputum smear microscopy (Aim 1); if quantitative amplification of antigen 85B mRNA, a transcript associated both with mycobacterial viability and with TB treatment effects, can predict treatment failure early in the course of disease (Aim 2); and if the oral wash plus nucleic acid test is cost-effective for diagnosing TB in this high-burden setting. (Aim 3) Dr. Davis will use the existing infrastructure of the International HIV-associated Opportunistic Pneumonias study (1R01 HL090335-01) to enroll and follow 300 HIV-infected TB suspects. This research will form the basis for a future randomized trial comparing conventional and novel diagnostic tests for TB diagnosis in this region. Public Health Impact: We are studying if fast new tests that do DNA fingerprinting on salt water mouthwashes are cheap and accurate for diagnosing tuberculosis in the lungs of patients with HIV. We are also trying to find out if a similar test can tell if these patients are getting better once they start treatment.